title: Prediction of placebo response in 2 clinical trials of lisdexamfetamine dimesylate for the treatment of ADHD.
abstract: OBJECTIVE
  To search for predictors of placebo response in clinical trials of lisdexamfetamine dimesylate for the treatment of DSM-IV-TR-defined attention-deficit/hyperactivity disorder (ADHD) in children and adults.
  
  
  METHODS
  We used data from 2 clinical trials: (1) a 4-week, phase 3, multicenter, randomized, double-blind, forced-dose, parallel-group study of children aged 6 to 12 years with ADHD (n = 290) and (2) a 4-week, randomized, double-blind, placebo-controlled, parallel-group, forced-dose titration study in adult subjects, aged 18-55 years with ADHD (n = 420). Response and remission were defined using the ADHD Rating Scale-IV and the Clinical Global Impressions-Improvement scale.
  
  
  RESULTS
  Symptom remission was inversely correlated with baseline severity in both children and adults (P < .001), with less robust effects seen for response. The time to response and remission was delayed in adult subjects prescribed placebo versus lisdexamfetamine dimesylate, while response time in children was also significantly slower with placebo versus lisdexamfetamine dimesylate (P < .01). We found little evidence that demographic factors, prior pharmacotherapy, the emergence of adverse events during the trial, or changes in ADHD symptoms from the screening to baseline assessments predicted placebo response. Certain comorbid medical symptoms reduced the response and remission rates to placebo in children (P < .001) and adults (P < .001).
  
  
  CONCLUSIONS
  In both children and adults, baseline symptom severity was the most consistent predictor of remission with placebo while the temporal profile of response reliably differentiated placebo from medication responders. Placebo effects are most likely to be minimized in shorter trials enrolling more severely impaired subjects. The impact of medical and psychiatric comorbidities on placebo response merits further investigation.
  
  
  BACKGROUND
  clinicaltrials.gov identifiers NCT00556296 and NCT00334880.
authors.affiliation: Department of Psychiatry, State University of New York at Buffalo, USA.
authors.forename: James G
authors.initials: JG
authors.lastname: Waxmonsky
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Waschbusch
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Glatt
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Faraone
mesh_terms: D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D002648:Child; D015897:Comorbidity / Q000639:trends; D003913:Dextroamphetamine / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005544:Forecasting; D006801:Humans; D000069478:Lisdexamfetamine Dimesylate; D008875:Middle Aged; D010919:Placebos / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000697:Central Nervous System Stimulants; D010919:Placebos; D000069478:Lisdexamfetamine Dimesylate; D003913:Dextroamphetamine